Asthma is a heterogeneous inflammatory disorder of the airways characterized by chronic deregulated inflammation, bronchial hyperreactivity, and by symptoms of recurrent wheezing, coughing, and shortness of breath. Its prevalence has increased considerably over the past three decades, particularly in Western countries. Asthma is a major public health problem that affects 300 million people worldwide. Classically, the airway smooth muscle cells contribute to the pathogenesis of asthma mainly through its contractile properties: airway hyperresponsiveness (AHR), one of the main characteristics in asthma, refers to excessive contractile response of airway smooth muscle cells. The degree of AHR correlates with asthma severity and the need for therapy.
Regular treatment is composed by the inhalation of corticosteroids and long-acting beta2-adrenergic receptor agonists. However, severe asthma escapes to usual treatments or frequently requires higher doses. In acute asthma, two main classes of bronchodilators are available: short actin beta-2 agonists and anticholinergics. These drugs are rapidly effective in general. However in some cases as acute severe asthma they can be insufficient, so that new drugs acting through other pathways to reverse airways obstruction could help preventing the still elevated number of asthma deaths. The pathophysiology of asthma must therefore be better understood in order to identify new targets and design new treatments.
AHR is also observed in chronic obstructive pulmonary disease (COPD). COPD is characterized by airflow obstruction that is generally caused by chronic bronchitis, emphysema, or both. Commonly, the airway obstruction is incompletely reversible but most subjects do show a limited improvement in airway obstruction with treatment. In COPD, airway obstruction results from chronic and excessive secretion of abnormal airway mucus, inflammation, bronchospasm, and infection.
There is very little currently available treatment to alleviate symptoms of COPD, prevent exacerbations, preserve optimal lung function, and improve daily living activities and quality of life. Many subjects will use medication chronically for the rest of their lives, with the need for increased doses and additional drugs during exacerbations.
Thus, there is a need for additional treatment options in inducing bronchodilatation and managing airway hyper-responsiveness independently of airway inflammation in airway diseases, more particularly bronchoconstrictive disorders such as asthma or COPD.